Please use this identifier to cite or link to this item: doi:10.22028/D291-31052
Title: Cardiomyocyte-Specific Deletion of Orai1 Reveals Its Protective Role in Angiotensin-II-Induced Pathological Cardiac Remodeling
Author(s): Segin, Sebastian
Berlin, Michael
Richter, Christin
Medert, Rebekka
Flockerzi, Veit
Worley, Paul
Freichel, Marc
Camacho Londoño, Juan E.
Language: English
Title: Cells
Volume: 9
Issue: 5
Publisher/Platform: MDPI
Year of Publication: 2020
Free key words: calcium
cardiac remodeling
cardiac function
Orai1 proteins
neurohumoral stimulus
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Pathological cardiac remodeling correlates with chronic neurohumoral stimulation and abnormal Ca2+ signaling in cardiomyocytes. Store-operated calcium entry (SOCE) has been described in adult and neonatal murine cardiomyocytes, and Orai1 proteins act as crucial ion-conducting constituents of this calcium entry pathway that can be engaged not only by passive Ca2+ store depletion but also by neurohumoral stimuli such as angiotensin-II. In this study, we, therefore, analyzed the consequences of Orai1 deletion for cardiomyocyte hypertrophy in neonatal and adult cardiomyocytes as well as for other features of pathological cardiac remodeling including cardiac contractile functionin vivo. Cellular hypertrophyinduced by angiotensin-IIin embryonic cardiomyocytes from Orai1-deficient mice was blunted in comparison to cells from litter-matched control mice. Due to lethality of mice with ubiquitous Orai1 deficiency and to selectively analyze the role of Orai1 in adult cardiomyocytes, we generated a cardiomyocyte-specific and temporally inducible Orai1 knockout mouse line (Orai1CM–KO). Analysis of cardiac contractility by pressure-volume loops under basal conditions and of cardiac histology did not reveal differences between Orai1CM–KO mice and controls. Moreover, deletion of Orai1in cardiomyocytesin adultmice did not protect them from angiotensin-II-induced cardiac remodeling, but cardiomyocyte cross-sectional area and cardiac fibrosis were enhanced. These alterations in the absence of Orai1 go along with blunted angiotensin-II-induced upregulation of the expression of Myoz2 and a lack of rise in angiotensin-II-induced STIM1 and Orai3 expression. In contrast to embryonic cardiomyocytes, where Orai1 contributes to the development of cellular hypertrophy, the results obtained from deletion of Orai1 in the adult myocardium reveal a protective function of Orai1 against the development of angiotensin-II-induced cardiac remodeling, possibly involving signaling via Orai3/STIM1-calcineurin-NFAT related pathways.
DOI of the first publication: 10.3390/cells9051092
Link to this record: urn:nbn:de:bsz:291--ds-310526
ISSN: 2073-4409
Date of registration: 22-Dec-2020
Description of the related object: Supplementary Materials
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professorship: M - Prof. Dr. Veit Flockerzi
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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